Project Summary/Abstract (Cells and Tissue Core) The Cells and Tissue Core was established to provide well-differentiated airway epithelial models for studies on the pathophysiology of cystic fibrosis (CF) and for in vitro gene transfer experiments. These models have been critical for dissecting various aspects of CF pathophysiology, including defects in ion transport, innate immunity, and inflammatory responses to bacterial challenge. Furthermore, these differentiated airway models are extremely useful for evaluating viral vectors prior to their use in animal models, as well as for studying the biology of viral infection and mechanisms that limit the efficacy of gene transfer from the apical membrane. Critical to these studies is the ability to generate air-liquid interface cultures of epithelia from CF and non-CF humans, pigs, ferrets, and mice. The Cells and Tissue Core also electrophysiologically assesses CFTR complementation in these models following gene transfer. Despite the differences in airway biology between mice and humans with respect to CF, mouse airway epithelial models have been extremely useful for studying airway stem cell biology, given the wide availability of conditional knockout and reporter strains of mice. The Core has also played a key role in developing new technologies and methods for amplifying, differentiating, and genetically manipulating airway epithelial cells from each of the above species. Recent developments include applying ROCK inhibitor to more efficiently grow both proximal and distal airway progenitors on irradiated fibroblasts. Despite the development of CF pig and ferret models, researchers continue to be highly dependent on the availability of human non-CF and CF differentiated airway epithelia. In this context, the Cells and Tissue Core organizes the acquisition of transplant lungs from several sources, and centralizes the distribution of these precious resources. The Core also trains investigators at the University of Iowa and other institutions in methods for developing in vitro airway model systems.